Molecular structure and assembly of the tight junction.
Polarized epithelial cells separate two extremely different cellular milieus. The tight junction (TJ) is the most apical component of the junctional complex and serves as the permeability barrier between these environments. The tight junctional complex appears to be a dynamic and regulated structure. Some of its protein components have been identified and include the transmembrane protein occludin. Nontransmembrane proteins on the cytosolic leaflet including ZO-1, ZO-2, cingulin, 7H6, and several unidentified phosphoproteins are also believed to be part of the TJ. Interactions of some of these proteins with the actin cytoskeleton are a major determinant of TJ structure and may also play a role in the regulation of TJ assembly. Recent progress using the "calcium switch" and the "ATP depletion-repletion" model of TJ formation offers new insight regarding how these structures form. TJ biogenesis appears to be regulated, in part, by classic signal transduction pathways involving heterotrimeric G proteins, release of intracellular Ca2+, and activation of protein kinase C. Although many of the details of the signaling pathways have yet to be defined, these observations may provide insight into how TJs form during tubular development. Furthermore, it may be possible to suggest potential therapeutic targets for intervention in a variety of diseases (e.g., ischemia, toxic injury to the kidney and other epithelial tissue) where TJ integrity has been compromised and reassembly is required.
Denker
B M
BM
Renal Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Nigam
S K
SK
D000818:Animals; D004847:Epithelial Cells / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000737:chemistry* / Q000502:physiology*; D008958:Models, Molecular; D008961:Models, Structural; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D019108:Tight Junctions / Q000502:physiology* / Q000648:ultrastructure*
D008565:Membrane Proteins; D010750:Phosphoproteins